Calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEIs) are widely used for the treatment of hypertension and related diseases and conditions.
Amlodipine, a calcium channel blocker, and its salts are disclosed in U.S. Pat. No. 4,879,303. Further the maleate salt of amlodipine as set forth in U.S. Pat. No. 4,572,909.
Benazepril, an angiotensin converting enzyme inhibitor, its salts and benazepril at are disclosed in U.S. Pat. No. 4,410,520.
U.S. Pat. No. 6,162,802 claims pharmaceutical composition consisting of amlodipine and benazepril such that the two drugs are physically separated from each other. In the specifications of this patent, the inventors disclose that physical separation of amlodipine and benazepril is necessary as they are incompatible substances. Physical separation of the two drugs has been shown to be achieved in a number of ways; coating pellets of one active, before incorporating into a tablet of the other, separately coating pellets of each active and then filling in a capsule, coating pellets of one active and filling in a capsule with powder of the other active, microencapsulating each active separately in order to ensure that the two drugs do not come in contact and then blending together for use in a tablet or capsule, use of a dual or multiple compartment transdermal device, etc.
Physical separation of the two components however, not only requires complicated processing, it also has inherent risks and complications. For example, chance contamination of one drug with the other during preparation would lead to degradation products. Therefore a need was felt to find ways to over come the problem using alternate means of stabilization.
It has now been surprisingly found that a stable composition of a combination of amlodipine and benazepril can be prepared using excipients other than alkali and alkaline earth metal carbonates and phosphates, resulting in a product, which shows improved stability, thus avoiding the need of physical separation of the two drugs.